# Understanding how activity drives diverse spine structural interactions

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $388,560

## Abstract

Abstract
Brain circuits can be structurally rearranged with experience, and synaptic connections can grow and be
eliminated, even in adults. We have shown that activity at specific inputs can lead to the production of new
proteins, promoting either long lasting growth of single spines, or cooperation and competition between multiple
synapses following potentiation. The balance between such interactions during structural plasticity can be the
basis for plasticity at the circuit level, which allows for the rewiring of inputs within a dendritic domain. However,
in order to be able to achieve such reorganization, mechanisms for strengthening co-active inputs as well as
those that would achieve weakening and elimination of inputs would be required. The synthesis of new proteins
is crucial for the long term storage of information, long lasting synaptic potentiation and structural plasticity. Of
interest, this is also necessary for long lasting forms of synaptic depression, while much less is understood about
the bidirectional regulation of structural plasticity. In addition to these Hebbian plasticity processes, additional
forms of plasticity, such as homeostatic modulation, impact the plasticity capacity of dendritic branches.
Homeostatic plasticity can scale synaptic currents, as well as spine structures, and can interact with Hebbian
plasticity to elicit plasticity at non active neighbors. In addition, neurons receive diverse patterns of activity at
their inputs, and it is unknown how these effect structural plasticity, or whether they are more or less likely to be
subject to complex integration between co-active inputs. Therefore, using two-photon imaging and glutamate
uncaging to stimulate and monitor plasticity at single spines or defined groups of spines, we will investigate the
relationship between different forms of plasticity and spine structural changes. Specifically, we will determine
whether synaptic depression can be induced at single inputs, what are the structural outputs of this form of
plasticity, and whether protein synthesis dependent depression at multiple inputs can undergo competition.
Further, we will investigate the structural plasticity rules of interactions between different forms of activity, such
as Hebbian and homeostatic plasticity, when they coincide within a dendritic domain at multiple inputs. Beyond
these forms of plasticity, we will also investigate non-regular patterns of activity, that follow instead a Poisson
distribution, in order to build an understanding of how individual inputs process a diversity of activity, how they
integrate this with events at co-active neighbors, and what are the structural correlates of these forms of plasticity.
These experiments will allow us to investigate with unprecedented precision at the molecular, subcellular and
circuit level the dynamics of synaptic interactions, and how they contribute to the building and refinement of
neural circuits necessary for cognitive function.

## Key facts

- **NIH application ID:** 9974133
- **Project number:** 1R01NS112485-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Inbal Israely
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $388,560
- **Award type:** 1
- **Project period:** 2020-03-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974133

## Citation

> US National Institutes of Health, RePORTER application 9974133, Understanding how activity drives diverse spine structural interactions (1R01NS112485-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9974133. Licensed CC0.

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